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Biomedical subjects

A Larsen

Publications and source records attributed to A Larsen.

At least 37 records · Page 2Linked to original sources

Management of the upper limb with botulinum toxin type A in children with spastic type cerebral palsy and acquired brain injury: clinical implications.

The aim of this article is to describe our clinical experience in treating muscle imbalance in 49 children with spastic upper extremity involvement. We discuss four cohorts of children treated with botulinum toxin type A (BTX-A), each with different treatment objectives. In the first group, 27 children were treated for functional improvement and, of these, 23 had a positive effect, while four had no objective benefit. In the second group, eight children were treated for purposes of presurgical planning; of these, four were referred for surgery, three continued with serial treatment and one child did not benefit from injection. The third group comprised six children who were treated to improve posture and care: in this group, four children demonstrated clear benefit and two children lost some function subsequent to injection. Finally, a fourth group of seven children were treated after acquired brain injury (three with severe tetraplegia, four with hemiplegia). In this group, all children experienced spasticity relaxation and two children with hemiplegia also gained functional benefit. In terms of adverse events, deterioration of upper extremity function was poorly tolerated but limited to the first 1--3 weeks postinjection. Grip strength or thumb grip were diminished if too high doses were used. Overall, our results with BTX-A were rewarding in children with no fixed contracture, good motor learning capacity and high motivation to train. Additionally, BTX-A treatment has proven valuable for counteracting spasticity in children with acquired brain injury. This treatment modality may not, however, be an appropriate treatment option for all children with severe upper extremity spasticity, due to the shorter duration of effect and the potential reduction in functional abilities seen in this cohort. In all cases, the selection of muscles to be treated needs careful clinical assessment. Dynamic EMG analysis should be performed whenever required to aid muscle selection, especially in children with spasticity combined with dystonia. Evaluation of M-responses suggests that for the forearm muscles, doses of BTX-A above 1.5 U/kg/muscle should not be used.

Adolescent↗

Electroencephalography in juvenile neuronal ceroid lipofuscinosis: visual and quantitative analysis.

Fourteen patients with a confirmed diagnosis of juvenile neuronal ceroid lipofuscinosis (JNCL) (aged 6-12.5 years at the beginning of the study) were prospectively followed for 5 years. An electroencephalogram (EEG) was recorded and analysed both visually and quantitatively and a neuropsychological examination was performed once a year. In addition, a cross-sectional EEG study of 32 patients aged 5-27 years was performed. The EEG was often normal before the age of 9 years, and thereafter a progressive background abnormality and increase in paroxysmal activity took place. The EEGs were significantly slower than those of the controls, and the speed of slowing of EEG correlated to the decrease in intelligence quotients (IQ). Quantitative analysis was superior to visual analysis in detecting the deterioration of the background activity. The best parameter describing this was the fast/slow ratio. Peak frequency, percentage of theta and the fast/slow ratio correlated with IQ.

Adolescent↗

Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine.

Radiographic disease progression with leflunomide and sulfasalazine treatment was assessed in rheumatoid arthritis patients in a double-blind trial that was placebo controlled for the first 6 months. Completers at 6 months opted to continue on 12- and 24-month double-blind extensions; patients in the placebo group were switched to sulfasalazine. Changes in Larsen scores were assessed in evaluable patient cohorts at 6 (n=228), 12 (n=136), and 24 (n=65) months. Changes in Larsen scores and erosive joint counts with leflunomide and sulfasalazine at 6 months showed significantly less radiographic progression than placebo. Sustained retardation of radiographic progression was seen in the 24-month intent-to-treat cohorts (delta Larsen scores: leflunomide -0.07, sulfasalazine -0.03). Changes in erosive joint counts within the 24-month leflunomide cohort suggest halting of disease progression for patients who continued in the study for 2 years (leflunomide -0.92, sulfasalazine 0.80). Leflunomide was well tolerated with no unexpected adverse events during the 2-year period. This study demonstrates that slowing of disease progression with leflunomide, observed as early as 6 months, is maintained long term in patients who complete 2 years of treatment.

Adult↗

Expression of Babesia equi merozoite antigen 1 in insect cells by recombinant baculovirus and evaluation of its diagnostic potential in an enzyme-linked immunosorbent assay.

The gene encoding the entire Babesia equi merozoite antigen 1 (EMA-1) was inserted into a baculovirus transfer vector, and a recombinant virus expressing EMA-1 was isolated. The expressed EMA-1 was transported to the surface of infected insect cells, as judged by an indirect fluorescent-antibody test (IFAT). The expressed EMA-1 was also secreted into the supernatant of a cell culture infected with recombinant baculovirus. Both intracellular and extracellular EMA-1 reacted with a specific antibody in Western blots. The expressed EMA-1 had an apparent molecular mass of 34 kDa that was identical to that of native EMA-1. The secreted EMA-1 was used as an antigen in an enzyme-linked immunosorbent assay (ELISA). The ELISA differentiated B. equi-infected horse sera from Babesia caballi-infected horse sera or normal horse sera. The ELISA was more sensitive than the complement fixation test and IFAT. These results demonstrated that the recombinant EMA-1 expressed in insect cells might be a useful diagnostic reagent for detection of antibodies to B. equi.

Animals↗

Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine.

OBJECTIVE: Recent studies have demonstrated the short term efficacy of leflunomide. This study evaluates the efficacy and safety of leflunomide and sulfasalazine in rheumatoid arthritis over a two year follow up period. METHODS: 358 patients with rheumatoid arthritis in a double blind trial were randomly allocated to receive either leflunomide 20 mg/day, placebo, or sulfasalazine 2 g/day. Those completing six months of treatment (n=230) were given the option to continue in 12 (n=168) and 24 (n=146) month double blinded extensions; the placebo group switched to sulfasalazine. This report compares efficacy and safety of leflunomide with sulfasalazine in the 6, 12, and 24 month patient cohorts. RESULTS: The efficacy seen at six months was maintained at 12 and 24 months. Twenty four month cohorts on leflunomide showed significant improvement compared with sulfasalazine in doctor (-1.46 v -1.11, p=0.03) and patient (-1.61 v -1.04, p<0.001) global assessments, ACR20% response (82% v 60%, p<0.01), and functional ability (Deltamean HAQ -0.65 v -0.36, p=0.0149; DeltaHAQ disability index -0.89 v -0.60, p=0.059). Improvement in other variables was comparable for the two drugs, including slowing of disease progression. Improved HAQ scores in 6, 12, and 24 month leflunomide cohorts were seen in both non-responders (24%, 29%, 35%, respectively v sulfasalazine 8%, 10%, 27%) and ACR20% responders (leflunomide 63%, 62%, 66% v sulfasalazine 50%, 64%, 44%). Leflunomide is well tolerated at doses of 20 mg. No unexpected adverse events or late toxicity were noted during the two year period. Diarrhoea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION: These long term data confirm that leflunomide is an efficacious and safe disease modifying antirheumatic drug.

Adult↗

Sleep alterations in juvenile neuronal ceroid-lipofuscinosis.

In juvenile neuronal ceroid-lipofuscinosis (JNCL), sleep disorders are common. The purpose of this study was to investigate the sleep structure of 28 patients with JNCL compared with healthy controls subjects and to clarify the pathophysiology underlying the sleep disturbances in these patients. Each of 28 patients with JNCL (age range = 6-27 years), with or without sleep complaints, underwent one night of polysomnography. Electroencephalographic, electro-oculographic, electromyographic, and electrocardiographic findings were recorded. Sleep was scored and analyzed visually. The sleep parameters of the patients were compared with those of healthy control subjects. In most of the patients, the total sleep time, sleep efficiency, and percentages of rapid eye movement (REM) and non-REM (NREM) stage 2 sleep were significantly decreased, and the percentages of NREM stage 1 and slow-wave sleep and the number of nocturnal awakenings significantly increased. The percentage of NREM stage 1 and the number of awakenings increased with age and clinical stage. Paroxysmal epileptiform activity during light sleep (NREM stages 1-2) and high-amplitude delta-wave activity with intermingled sharp waves during slow-wave sleep were characteristic of the recordings. The present study revealed that in patients with JNCL, sleep is consistently altered.

Adolescent↗

The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins.

OBJECTIVES: To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. SETTING: In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. SUBJECTS: Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. INTERVENTIONS: The women were randomized to HRT, i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. MAIN OUTCOMES: Effects on lipids and lipoproteins. RESULTS: After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. CONCLUSIONS: In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Administration, Cutaneous↗

Botulinum toxin injection as an adjunct when planning hand surgery in children with spastic hemiplegia.

The usefulness of botulinum toxin A treatment when planning hand surgery in eight children with spastic hemiplegia was evaluated. The hand function of the children was assessed before and after treatment using a test battery consisting of quantitative and qualitative functional assessment. The results of preoperative botulinum treatment supported surgical intervention in four children and serial botulinum treatment in three children. In one child, the preoperative botulinum treatment provided no additional information. We conclude that preoperative botulinum A treatment in most children with spastic hemiplegia, for whom hand surgery is being considered, identifies the patients who would not benefit from the planned surgery or for whom the functional benefit would probably not outweigh the burden of surgical procedure and postoperative rehabilitation.

Adolescent↗

Database developed to record and evaluate computer aided endonasal surgery results.

Computer aided surgery has been used in the Department of Otolaryngology--Head & Neck Surgery, Rigshospitalet, Copenhagen since October 1998, and is now a regular supplement to conventional functional endonasal sinus surgery (FESS) and management of anterior skull base lesions. This technique was designed to enhance surgical precision and thoroughness and to reduce complications. Since this is a new technique, the clinical findings and surgical outcome are prospectively collected in a database. Results for conventional FESS are entered in the same database for comparison. The aim of this study is to present a standardized Danish database.

Databases as Topic↗

Brain activation during mental transformation of size.

Visual comparison between different-sized objects with respect to shape can be done by encoding one of the objects as a mental image, transforming the image to the size format of the other object, and then testing for a match (Bundesen, C., & Larsen, A. [1975]. Visual transformation of size. Journal of Experimental Psychology: Human Perception and Performance, 1, 214-220). To identify the brain structures implicated in mental transformation of size, we measured the distribution of regional cerebral blood flow (rCBF) by positron emission tomography (PET) in 12 normal subjects who compared random stimulus patterns with respect to shape regardless of variations in size in a one-back match-to-sample paradigm. Each subject was PET-scanned 12 times during repetitive injections of H(2)(15)O. In one condition (three scans), all stimulus patterns were small. In a second condition (three scans), all stimuli were large. In the third condition (six scans), the stimuli alternated between small and large. Mental transformation of size should occur in the alternating-size condition but not in the fixed-size conditions. As expected, behavioral measures (reaction time [RT], d', beta) were nearly the same for the two fixed-size conditions but mean RT was longer and d' smaller in the alternating-size condition. Changes in rCBF specific to mental transformation of size were estimated by contrasting the alternating-size with the fixed-size conditions by use of statistical parametric mapping (SPM96) at a threshold of p <. 05 corrected for multiple comparisons. The detected brain structures implicated in mental transformation of size were primarily located in the dorsal pathways, comprising structures in the occipital, parietal, and temporal transition zone (predominantly in the left hemisphere), posterior parietal cortex (bilaterally), area MT/V5 (left), and vermis (bilaterally). Contrasts between the two fixed-size conditions showed significant effects in only the occipital cortex.

Adult↗

Assessing radiographic status of rheumatoid arthritis: introduction of a short erosion scale.

OBJECTIVE: Although radiographs are an important marker of rheumatoid arthritis severity, no valid simple scoring method exists. Current scoring systems are cumbersome, difficult to learn, time consuming, and suitable only for experts. In addition, there is no "gold standard" for radiographic severity, so that it is impossible for the clinician, trialist, or researcher to place patients' scores along a continuum of radiographic severity. We investigated the scoring and scaling properties of radiographs read by the Larsen method, and we developed a shortened scale that can be placed in the perspective of a linear severity continuum. METHODS: A total of 3,538 paired hand radiographs obtained over a 24 year period were read by Larsen method and evaluated by Rasch analysis. By iterative methods the number of joints was reduced so that proper fitting, scaling, and dimensionality were obtained. The shortened scale was then tested against the full Larsen scale to determine its ability to detect radiographic progression. RESULTS: A scale consisting of 6 joints on each hand (3 wrist areas and 3 metacarpophalangeal joints) performed as well as the full 28 joint Larsen score, and had improved fit and scaling properties. This Short Erosion Scale (SES) also performed as well as the Larsen score in measuring radiographic progression as measured by comparative effect sizes. In addition, a nomogram was developed to translate SES scores into radiographic severity scores according to a Rasch logit scale. CONCLUSION: We developed a Short Erosion Scale by reducing the number of joints evaluated in the Larsen method from 28 to 12. The scale is at least as sensitive in detecting change as the full Larsen scale. SES fits the Rasch model and is hierarchical and generally well spaced. Graphs and nomograms are available so that intrinsic radiographic severity can be documented. This scale is suitable for use in clinical practice and observational studies, and may be appropriate for clinical trials as well.

Arthritis, Rheumatoid↗

[Life situation of patients with ileoanal anastomosis].

Ileal pouch-anal anastomosis is an alternative to ileostomy for patients with ulcerative colitis. Results of a questionnaire survey answered by 155 patients organised in a support group are presented. Consequences of the operation were mainly faecal incontinence, experienced by half of the group in the daytime, and frequent defaecations (5-7 per day, 1-2 per night). One half of the patients used medication every day to decrease the number of defaecations. 64% had changed their diet, while social and physical activities were reduced for 43% of the patients. Changes in lifestyle after the operation lead to increased expenses for 70% of the group. Women were more often incontinent than men and experienced it as a serious problem, and more women than men had changed their dietary habits. The quality of sleep was inferior to that of the preoperative period for 47% of the patients. 50% felt restricted in daily life activities due to frequent defaecations. These patients are living with a concealed disability. In spite of this, their assessments of self-esteem, health and quality of life were mainly positive.

Adolescent↗

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group.

BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.

Algorithms↗

Neurological and psychological findings in patients with Cohen syndrome: a study of 18 patients aged 11 months to 57 years.

Our purpose was to perform the first systematic neurological, neurophysiological and psychological study of 18 patients with Cohen syndrome (MIM no 216550), aged 11 months to 57 years (median 27 years). All the patients had the essential features of this syndrome, i.e., typical facial and structural findings, mental retardation, microcephaly, ophthalmologic symptoms, granulocytopenia and a cheerful psychic disposition. Children with the syndrome were considered normal at birth, but upwards of 6 to 12 months, psychomotor retardation became obvious. The first symptoms were microcephaly, which manifested itself by the age of 6 months to 1 year, as well as hypotonia and delayed developmental milestones. Cohen children learned to walk at 2 to 5 years of age. Language development varied markedly. Neurological symptoms did not progress. All patients had normal EMGs. The three youngest (aged 11 months, 3 and 5 years) had normal EEGs, whereas the remainder had low-voltage EEGs. No irritative spikes or epileptoformic foci were found. Nine patients had quick beta transients. Of the 18 patients examined, 4 were profoundly, 11 severely, 1 moderately and 2 mildly retarded. On the AADM scale, Cohen patients had high scores in the positive domains, viz., self-direction, responsibility and socialisation. Maladaptive behaviour, on the other hand, was almost completely absent, except for stereotyped behaviours and odd mannerisms. Withdrawal, sexually aberrant behaviour, untrustworthy and rebellious behaviour as well as antisocial behaviour were rare. These findings are consistent with the cheerful and sociable disposition characteristic of those with Cohen syndrome.

Activities of Daily Living↗

Biotransformation of nonionic X-Ray contrast agents In vivo and In vitro.

Liposomes loaded with the nonionic iodinated contrast agent iodixanol were injected i.v. into monkeys, rats, and dogs, and liver samples were analyzed by HPLC and mass spectrometry. Two metabolites (M1 and M2), with UV spectra identical to those of the iodixanol isomers (exo and endo) and with a mass increase of 162 compared with iodixanol, were detected. Incubations of iodixanol-liposomes or iodixanol in rat liver homogenates resulted in large amounts of iodixanol metabolites, whereas no metabolites were formed in other organ or tissue homogenates. Four groups of unidentified HPLC peaks were detected: M1 and M2 with a relative retention similar to the metabolite peaks of the in vivo samples, and in addition the minor M3 and M4. UV spectrum analysis indicated that M1 and M3 were structurally related to the iodixanol exo-isomer, whereas M2 and M4 were related to the endo-isomer. Mass spectrometry techniques indicated that the metabolites were conjugates containing one or two hexose residues, which by carbohydrate analysis and experiments with concanavalin A-Sepharose and alpha- and beta-glucosidase were shown to be glucose residues bound to iodixanol through O-alpha1-glycoside-like linkages. Metabolites with similar mass increments also were detected for several other nonionic contrast agents after in vitro incubations in liver homogenates. In conclusion, M1 and M3 are conjugates of the iodixanol exo-isomer with one and two glucose adducts, respectively. M2 and M4 are similar conjugates of the iodixanol endo-isomer. This is the first report on hepatic biotransformation of this class of X-ray contrast agents.

Animals↗

Specific detection and quantification of palmitoyl-stearoyl-phosphatidylserine in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry.

A narrow-bore normal-phase high-performance liquid chromatography (HPLC) method was developed for separation of phospholipid classes using an HPLC diol column and a gradient of chloroform and methanol with 0.2% formic acid titrated to pH 5.3 with ammonia. The HPLC system was coupled on-line with an electrospray mass spectrometry (ES-MS) or electrospray tandem mass spectrometry (ES-MS-MS) system and the separation of several major phospholipid classes was shown. The molecular species of some phospholipid classes in human blood were qualitatively determined. A method was further developed for specific determination of a molecular species from phosphatidylserine, palmitoyl-stearoyl-phosphatidylserine (PSPS), in human blood using HPLC-ES-MS. The analyses were performed by single ion monitoring of the [M-H]- molecular ions of PSPS and an internal standard, dipalmitoyl-phosphatidylserine. The limit of quantification of the method was 1.2 ng of PSPS. The calibration curve ranged from 0.12 to 5.81 microg/ml of PSPS dissolved in the mobile phase. The curve was fitted to a second-order polynomial equation and found to be highly reproducible. Analysis of control samples was found to be reproducible with a between-series precision below 9.2% R.S.D. The amount of endogenous PSPS in human blood was determined in 13 subjects and found to range from 1.73 to 3.09 microg/ml. The identity of endogenous PSPS was confirmed by HPLC-ES-MS-MS.

Ammonia↗

Study of mechanisms involved in the collision-induced dissociation of carboxylate anions from glycerophospholipids using negative ion electrospray tandem quadrupole mass spectrometry.

The collision-induced dissociation of the carboxylate anions from human blood phosphatdilycholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidic acid (PA) containing the C18:0 (sn-1) and C20:4 (sn-2) fatty acyl residues was studied using normal phase liquid chromatography coupled with negative ion electrospray tandem mass spectrometry. The product ion peak area ratio of C18:0 to C20:4 was calculated for each phospholipid species and was found to increase with increasing collision energy for all classes. For the phospholipids with a net neutral charge (PE, PC) there was a preferential loss of the sn-2 carboxylate anion (C20:4) at low collision energy, while at higher energy there was a preferential loss of the sn-1 carboxylate anion (C18:0). For the phospholipids with a net negative charge (PI, PA, PS) the intensity of the sn-1 carboxylate anion peak was equal to or higher than the sn-2 carboxylate anion peak at the energies measured. At a given collision energy the product ion peak area ratio decreased in the order PA > or = PS > PI. Studying PS and PE species at different collision energies, it was found that for both classes the increase in the abundance ratio with increasing collision energy was largely dependent on the chain length and degree of unsaturation of the sn-2 acyl chain.

Carboxylic Acids↗